CN105560236A - Pharmaceutical composition containing ginkgolide B and pseudo-peptide thrombin inhibitor and preparation method and application of pharmaceutical composition - Google Patents
Pharmaceutical composition containing ginkgolide B and pseudo-peptide thrombin inhibitor and preparation method and application of pharmaceutical composition Download PDFInfo
- Publication number
- CN105560236A CN105560236A CN201510714240.2A CN201510714240A CN105560236A CN 105560236 A CN105560236 A CN 105560236A CN 201510714240 A CN201510714240 A CN 201510714240A CN 105560236 A CN105560236 A CN 105560236A
- Authority
- CN
- China
- Prior art keywords
- ginkalide
- dabigatran etcxilate
- pharmaceutical composition
- compositions
- weight proportion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a pharmaceutical composition containing ginkgolide B. The pharmaceutical composition comprises the ginkgolide B and pseudo-peptide thrombin inhibitor. The invention further provides a preparation method and application of the pharmaceutical composition. The pharmaceutical composition has the advantages that the ginkgolide B and the pseudo-peptide thrombin inhibitor are combined to achieve a synergic effect, and the pharmaceutical composition is excellent in anticoagulation effect, low in side effect and promising in clinical application prospect; the pharmaceutical composition is novel in prescription, simple in component, clear in action mechanism, evident in curative effect, less prone to tolerance generating and capable of achieving large-scale industrial production.
Description
Technical field
The present invention relates to the pharmaceutical composition of a kind of bilobalide-containing B.
Background technology
Dabigatran etcxilate is the oral anticoagulation thing direct thrombin inhibitor (DTIs) of new generation of forefront, chemical name: Beta-alanine, N-[[2-[[[4-[[[(hexyloxy) carbonyl] is amino] iminomethyl] phenyl] is amino] methyl]-1-methyl isophthalic acid H-benzimidazole-5-base] carbonyl]-N-2-pyrimidine-, ethyl ester, mesylate.Chemical molecular formula: C
34h
41n
7o
5cH
4o
3s, for apoplexy and the systemic embolism of medicine for preventing nonvalvular atrial patient.There is apoplexy and the systemic embolism (SEE) of adult's nonvalvular atrial fibrillation patient of following one or more risk factor in prevention: previously once had apoplexy, transient ischemic attack or systemic embolism; Left ventricular ejection fraction <40%; Symptoms accompanied heart failure, sick association (NYHA) cardiac functional grading >=2 grade of New York Heart; Age >=75 years old; Age >=65 years old, and with following arbitrary disease: diabetes, coronary heart disease or hypertension.
Clinical research shows, application dabigatran etcxilate has untoward reaction, and modal untoward reaction is hemorrhage, the side effect of other mainly gastrointestinal reverse side, comprise dyspepsia, nauseating, epigastrium pain, digestive tract hemorrhage and diarrhoea etc., cause the probability of myocardial infarction in addition.
Prevent about dabigatran etcxilate at one in the key research of the effect of apoplexy and SEE in patients with atrial fibrillation, amount to 12,042 routine patient and accept dabigatran etcxilate treatment.Wherein 6,059 routine patient accepts each 150mg of dabigatran etcxilate, the treatment of twice every day, and 5,983 routine patients accept each 110mg, the treatment of twice every day.Have 22% patients with atrial fibrillation (the longest treatment time reaches 3 years) accepting apoplexy or SEE prevention and occur untoward reaction.The untoward reaction the most often reported is hemorrhage, and in various degree hemorrhage occurs about 16.5% patients with atrial fibrillation accepting apoplexy and SEE prophylactic treatment.Although occurrence frequency is very low in clinical trial, massive hemorrhage or severe haemorrhage still likely occur, and the hemorrhage of any position likely can cause deformity, threat to life or mortality result.
Therefore, how when ensureing therapeutic effect, the use reducing dabigatran etcxilate is urgently to be resolved hurrily to reduce side effect.
Ginkalide B is the active component extracted from natural drug Folium Ginkgo, and its side effect is little, and active strong, be the strongest platelet activating factor antagonist found so far, may be used for anticoagulation, but price be high, the cost of Clinical practice is too high.
Summary of the invention
The object of the invention is to overcome that non-peptide batroxobin inhibitor develops in the alone side effect that produces in anticoagulation as dabigatran etcxilate a kind ofly has synergistic new pharmaceutical composition.
The invention provides the pharmaceutical composition of a kind of bilobalide-containing B, it is characterized in that: it contains ginkalide B and thrombin inhibitor.
Wherein, described thrombin inhibitor is non-peptide batroxobin inhibitor.Described non-peptide batroxobin inhibitor is dabigatran etcxilate.
Preferably, the weight proportion of described raw material is: ginkalide B 1-20 part and dabigatran etcxilate 50-500 part.Further preferably, the weight proportion of described raw material is: ginkalide B 5-15 part and dabigatran etcxilate 100-400 part.Still more preferably, the weight proportion of described each raw material is: ginkalide B 8-12 part and dabigatran etcxilate 150-300 part.Again further preferably, ginkalide B 10 parts and dabigatran etcxilate 200 parts.
Present invention also offers a kind of method preparing aforesaid pharmaceutical composition, it comprises the following steps:
S1: take raw material ginkalide B and thrombin inhibitor by component and weight ratio;
S2: after being mixed by raw material, adds pharmaceutically acceptable adjuvant and is prepared into pharmaceutically conventional pharmaceutical preparation.
Wherein, described pharmaceutically acceptable adjuvant comprises: starch, pregelatinized Starch, lactose, sucrose, Pulvis Talci, dextrin, cyclodextrin, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, glucose, meglumine, magnesium stearate, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, mannitol, sorbitol, xylitol, fibre plant oil, sodium benzoate, sodium salicylate, hydrochloric acid, citric acid, citric acid is received, sodium dihydrogen phosphate, sodium hydrogen phosphate, gelatin, lecithin, one in vitamin C or several.
Wherein, described pharmaceutical preparation comprises: tablet, capsule, soft capsule, oral liquid, granule, pill, drop pill, powder, unguentum, sublimed preparation, injection, suppository, patch, drop, spray, cream, suspensoid, tincture, Emulsion, aqueous injection, injectable powder, targeting preparation, slow releasing preparation, controlled release preparation.
Pharmaceutical composition described before present invention also offers is preparing the purposes in anticoagulation medicine.
Present invention also offers ginkalide B and thrombin inhibitor drug combination is preparing the application in anticoagulation medicine.
Wherein, described thrombin inhibitor is non-peptide batroxobin inhibitor.Described non-peptide batroxobin inhibitor is dabigatran etcxilate.
Preferably, the weight proportion of described raw material is: ginkalide B 1-20 part and dabigatran etcxilate 50-500 part.Further preferably, the weight proportion of described raw material is: ginkalide B 5-15 part and dabigatran etcxilate 100-400 part.Still more preferably, the weight proportion of described each raw material is: ginkalide B 8-12 part and dabigatran etcxilate 150-300 part.Again further preferably, ginkalide B 10 parts and dabigatran etcxilate 200 parts.
Pharmaceutical composition provided by the invention, because wherein containing ginkalide B and dabigatran etcxilate active component, can by different mechanism of action anticoagulations, ginkalide B significantly can promote that both anticoagulant functions of dabigatran etcxilate have the effect of Synergistic, Clinical practice can reduce thrombin inhibitor dose, increase drug effect, reduce costs, reduce side effect, for clinical research provides better selection.
Pharmaceutical composition novel formula of the present invention, component is simple, mechanism of action is clear and definite and evident in efficacy, not easily produce toleration, can industrialized great production be realized.
The present invention is by ginkalide B and dabigatran etcxilate conbined usage, the two can play synergistic function, anticoagulant, anticoagulant excellent effect, the consumption of dabigatran etcxilate can be reduced during clinical practice, and then reduce it and use the side effect brought in a large number, can also reduce the use amount of ginkalide B, reduce costs, potential applicability in clinical practice is excellent.
Obviously, according to foregoing of the present invention, according to ordinary technical knowledge and the customary means of this area, not departing under the present invention's above-mentioned basic fundamental thought prerequisite, the amendment of other various ways, replacement or change can also be made.
The detailed description of the invention of form by the following examples, is described in further detail foregoing of the present invention again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example.All technology realized based on foregoing of the present invention all belong to scope of the present invention.
Detailed description of the invention
Ginkalide B monomeric compound of the present invention, can obtain by buying commercially available prod, or obtain by bilobalide is carried out separation and purification in existing method; Dabigatran etcxilate also obtains by buying commercially available prod, also or by existing method is synthesized into.Through inspection, all monomeric compounds all conform to corresponding reference substance structure, and detect its purity all more than 95% through HPLC.
Embodiment 1
Ginkalide B 10 parts
Dabigatran etcxilate 200 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into pill.
Embodiment 2
Ginkalide B 5 parts
Dabigatran etcxilate 400 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into capsule or soft capsule.
Embodiment 3
Ginkalide B 20 parts
Dabigatran etcxilate 50 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into tablet.
Embodiment 4
Ginkalide B 15 parts
Dabigatran etcxilate 100 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into oral liquid.
Embodiment 5
Ginkalide B 10 parts
Dabigatran etcxilate 300 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into drop pill.
Embodiment 6
Ginkalide B 12 parts
Dabigatran etcxilate 150 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into spray.
Embodiment 7
Ginkalide B 1 part
Dabigatran etcxilate 500 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into aqueous injection or injectable powder.
Embodiment 8
Ginkalide B 10 parts
Dabigatran etcxilate 200 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into slow releasing preparation or controlled release preparation.
Embodiment 9
Ginkalide B 10 parts
Dabigatran etcxilate 200 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into targeting preparation.
Embodiment 10
Ginkalide B 10 parts
Dabigatran etcxilate 200 parts
Pharmaceutically acceptable customary adjuvant
By above-mentioned raw materials mix after, add pharmaceutically acceptable customary adjuvant conveniently technique be prepared into granule or suspensoid.
Below by the mode of test example, beneficial effect of the present invention is described:
Test example 1 ginkalide B and non-peptide batroxobin inhibitor combination suppress Platelet Aggregation in Rabbits effect experimentation
1 materials and methods
1.1 laboratory animal
Japan large ear rabbit 128, body weight (2.0 ± 0.2) kg, male and female half and half, are provided [the animal quality certification number: XCXK (Chongqing) 20020001] by Medical University Of Chongqing's Experimental Animal Center.
1.2 Experimental agents
Ginkalide B (self-control), dabigatran etcxilate (self-control), compositions 1 (ginkalide B: dabigatran etcxilate=10:200), compositions 2 (ginkalide B: dabigatran etcxilate=1:50), compositions 3 (ginkalide B: dabigatran etcxilate=1:500), compositions 4 (ginkalide B: dabigatran etcxilate=20:50), compositions 5 (ginkalide B: dabigatran etcxilate=20:500), compositions 6 (ginkalide B: dabigatran etcxilate=5:100), compositions 7 (ginkalide B: dabigatran etcxilate=5:400), compositions 8 (ginkalide B: dabigatran etcxilate=15:100), compositions 9 (ginkalide B: dabigatran etcxilate=15:400), compositions 10 (ginkalide B: dabigatran etcxilate=8:150), compositions 11 (ginkalide B: dabigatran etcxilate=8:300), compositions 12 (ginkalide B: dabigatran etcxilate=12:150), compositions 13 (ginkalide B: dabigatran etcxilate=12:300).
1.3 reagent and instrument
Platelet activating factor (PAF) (cayman, lot number: 011219) be dissolved in PH be 7.6 containing 0.25% bovin serum albumin Tris-NaCl solution in, final concentration is 3.6nmoL/L; Sodium citrate (Beijing biotech company of Zhong Shan Golden Bridge, lot number: 20130117) distilled water is made into the concentration of 3.8%; Rabbit β-thromboglobulin (β-TG) ELISA kit (FOCUS, lot number: 20130224), the rabbit platelet factor 4 (PF-4) ELISA kit (FOCUS, lot number: 20130301).TYXN-96 multifunctional intellectual blood pool instrument (development of Shanghai GM technical research institute); Scanning electron microscope S-3000N (HIT); ELX-800 microplate reader (Bao Te company of the U.S.).
1.4 grouping and medication
Japan large ear rabbit 128, be divided into 16 groups at random, often organize 8: (1) normal saline group, (2) ginkalide B group, (3) dabigatran etcxilate group, (4) compositions 1 group, (5) compositions 2 groups, (6) compositions 3 groups, (7) compositions 4 groups, (8) compositions 5 groups, (9) compositions 6 groups, (10) compositions 7 groups, (11) compositions 8 groups, (12) compositions 9 groups, (13) compositions 10 groups, (14) compositions 11 groups, (15) compositions 12 groups, (16) compositions 13 groups.Each group, all by Clinical practice approach, administration number of times administration, is used in conjunction 7 days.Each group of dosage is as following table:
| Group | Dosage | Daily number of times |
| Normal saline | 2ml | 1 |
| Ginkalide B | 5.0mg/kg | 1 |
| Dabigatran etcxilate group | 5.0mg/kg | 1 |
| Compositions 1 group | 5.0mg/kg | 1 |
| Compositions 2 groups | 5.0mg/kg | 1 |
| Compositions 3 groups | 5.0mg/kg | 1 |
| Compositions 4 groups | 5.0mg/kg | 1 |
| Compositions 5 groups | 5.0mg/kg | 1 |
| Compositions 6 groups | 5.0mg/kg | 1 |
| Compositions 7 groups | 5.0mg/kg | 1 |
| Compositions 8 groups | 5.0mg/kg | 1 |
| Compositions 9 groups | 5.0mg/kg | 1 |
| Compositions 10 groups | 5.0mg/kg | 1 |
| Compositions 11 groups | 5.0mg/kg | 1 |
| Compositions 12 groups | 5.0mg/kg | 1 |
| Compositions 13 groups | 5.0mg/kg | 1 |
1.5 detect platelet aggregation rate
After administration 7d, every animal hearts gets blood 10.5mL, separate 1.5mL blood plasma and get serum, the 3.8% sodium citrate 1:9 anticoagulant of all the other 9mL blood plasma, the centrifugal 10min of 800r/min, get supernatant and obtain platelet rich plasma (PRP), separate 100 μ LPRP for electron microscopic examination, all the other PRP are used for the detection of platelet aggregation rate; Remainder 3000r/min centrifugation 15min, gets platelet poor plasma (PPP).Regulate PRP with PPP, make PRP number of platelets 360 × 10
9/ L.Measure and be recorded in 10 μ LPAF derivant inductions lower 1min, 5min and max platelet rate.
1.6 platelets are observed
Isolated 100 μ LPRP are placed in silication EP pipe, add the gathering of the PAF induced platelet of 1 μ L, after effect 15min, PRP is placed in and is covered with in the copper mesh specimen holder of Formar film, hatch 10min, ultrapure water for 37 DEG C, 3% glutaraldehyde fixes 5min, clean with ultrapure water again, after the specimen natural drying on copper mesh, at the golden film of its plated surface one deck 20nm, ultramicroscope S-3000N scanning cellular morphology, observe 100 platelet, calculate various platelet proportion.Under Electronic Speculum, platelet typing comprises: (1) is circular: rounded or oval.Volume is little, and central authorities are fine and close, and core is large, and periphery zona pellucida is low narrow.(2) tree-like: to send single or multiple podocytic process from central dense area, elongated or lamellar, has branch sometimes.(3) shape is flattened: there are dense-core in central authorities, and peripheral zona pellucida is wider, and periphery is smooth or have little projection.(4) assemble shape: be often made up of to tens platelet several, aggregation differs in size, wherein visible platelet is interconnected, and some complete fusion are integral, and peripheral part platelet podocytic process is obvious.
The mensuration of PF-4 and β-TG contents level in 1.7 serum
In 1.5mL blood plasma, add the PAF of 1 μ L, the release of induction PF-4 and β-TG, blood plasma, in 4 DEG C of standing 4h, is got 200 μ L serum, is detected.Concrete operations are carried out according to test kit description, and microplate reader reads result data.
1.8 statistical procedures
Experimental result mean ± standard deviation
represent, carry out statistical analysis with SPSS18.0 software, the t inspection adopting two sample averages to compare carries out statistical analysis to each group of platelet aggregation rate, platelet PLA2 percent and PF-4 and β-TG content.P<0.05 is that difference has statistical significance.
2 results
2.1 platelet aggregation test results
Experimental result is as shown in table 1: table 1PAF induction platelet aggregation (
n=8)
Compare with normal saline group, * * p<0.01, * p<0.05
Under PAF induction, the max platelet rate that ginkalide B group, ginkalide B+dabigatran etcxilate are respectively organized is compared with normal saline group, all there is significance sex differernce (p<0.01, p < 0.05), illustrate that each compositions of the present invention all can effective anticoagulation, each group of platelet aggregation inhibition rate is significantly increased, and dabigatran etcxilate set of monomers does not produce change clearly compared with normal saline group, illustrate that ginkalide B and dabigatran etcxilate create synergism.
In each group of compositions, the best results of compositions 1, therefore, the proportioning of ginkalide B of the present invention and dabigatran etcxilate is preferably 10:200, under this proportioning, in compositions, ginkalide B consumption is few, the consumption of dabigatran etcxilate is many, it assembles suppression ratio but far away higher than the dabigatran etcxilate of compositions Isodose, and it is suitable with the gathering suppression ratio of the ginkalide B of compositions Isodose, illustrate in this ratio range, the synergistic function highly significant of ginkalide B and dabigatran etcxilate.
2.2 platelets testing results
Result is as shown in table 2:
After table 2 adds PAF each group platelet PLA2 compare (
n=8)
Compare with normal saline group, * * p<0.01, * p<0.05
Under the scanning electron microscope of 2000 times, be mainly observed four kinds of platelet PLA2: circular, tree-like, flatten shape and assemble shape.Under PAF induction, it is comparatively consistent that ginkalide B, ginkalide B+dabigatran etcxilate respectively organize Platelet Size, smooth surface, and accumulation type platelet is more rare, illustrates that each compositions of the present invention all can effective anticoagulation.And normal saline group platelet generation strong activation, platelet adhesion power strengthens, and can see red blood cell adhesion in platelet; Platelet PLA2 is irregular, volume increases, stretch out the pseudopodium outstanding in spore shape, assemble shape platelet counts increases.Dabigatran etcxilate set of monomers Platelet Size differs, and there is pseudopodium on surface, and gathering shape platelet is more, illustrates that ginkalide B creates synergism to dabigatran etcxilate.
In each group of compositions, the best results of compositions 1, therefore, the proportioning of ginkalide B of the present invention and dabigatran etcxilate is preferably 10:200, under this proportioning, in compositions, ginkalide B consumption is few, and the consumption of dabigatran etcxilate is many, its accumulation type platelet but far less than dabigatran etcxilate and the ginkalide B of compositions Isodose, the synergistic function highly significant of ginkalide B and dabigatran etcxilate.2.3 platelet PF-4 and β-TG testing result
Result is as shown in table 3:
Table 3 platelet PF-4 and β-TG testing result (
n=8)
Compare with normal saline group, * * p<0.01, * p<0.05
PF-4 and β-TG level reduces, and illustrates that platelet release function is suppressed.
Compared with normal saline group, ginkalide B, ginkalide B+dabigatran etcxilate are respectively organized PF-4 and β-TG level and are all significantly reduced (p<0.01, p<0.05), illustrate that each compositions of the present invention all can effective anticoagulation; And dabigatran etcxilate group does not significantly reduce, illustrate that ginkalide B has synergism to dabigatran etcxilate.
In each group of compositions, the best results of compositions 1, therefore, the proportioning of ginkalide B of the present invention and dabigatran etcxilate is preferably 10:200, and under this proportioning, in compositions, ginkalide B consumption is few, the consumption of dabigatran etcxilate is many, its PF-4, β-TG level but well below the dabigatran etcxilate of compositions Isodose, and is on close level with PF-4, β-TG of the ginkalide B of compositions Isodose, the synergistic function highly significant of ginkalide B and dabigatran etcxilate.
To sum up, the present invention, by ginkalide B and dabigatran etcxilate conbined usage, can play synergistic function, the pharmaceutical composition that ginkalide B of the present invention and dabigatran etcxilate form, can effectively anticoagulant, anticoagulation, excellent effect, potential applicability in clinical practice is excellent.
Claims (10)
1. a pharmaceutical composition of bilobalide-containing B, is characterized in that: it contains ginkalide B and non-peptide batroxobin inhibitor.
2. pharmaceutical composition according to claim 1, is characterized in that: described non-peptide batroxobin inhibitor is dabigatran etcxilate.
3. pharmaceutical composition according to claim 3, is characterized in that: the weight proportion of described ginkalide B and dabigatran etcxilate is: ginkalide B 1-20 part and dabigatran etcxilate 50-500 part.
4. pharmaceutical composition according to claim 4, is characterized in that: the weight proportion of described ginkalide B and dabigatran etcxilate is: ginkalide B 5-15 part and dabigatran etcxilate 100-400 part;
Preferably, the weight proportion of the two is: ginkalide B 8-12 part and dabigatran etcxilate 150-300 part; Further preferably, the weight proportion of the two is: ginkalide B 10 parts and dabigatran etcxilate 200 parts.
5. prepare a method for the pharmaceutical composition in Claims 1 to 4 described in any one, it comprises the following steps:
S1: take raw material ginkalide B and non-peptide batroxobin inhibitor by component and weight ratio;
S2: after being mixed by raw material, adds pharmaceutically acceptable adjuvant and is prepared into pharmaceutically conventional pharmaceutical preparation.
6. the pharmaceutical composition described in Claims 1 to 4 any one is preparing the purposes in anticoagulation medicine.
7. ginkalide B and non-peptide batroxobin inhibitor are preparing the application in anticoagulant combination medicine.
8. purposes according to claim 7, is characterized in that: described non-peptide batroxobin inhibitor is dabigatran etcxilate.
9. purposes according to claim 8, is characterized in that: the weight proportion of described ginkalide B and dabigatran etcxilate is: ginkalide B 1-20 part and dabigatran etcxilate 50-500 part.
10. purposes according to claim 9, is characterized in that: the weight proportion of described ginkalide B and dabigatran etcxilate is: ginkalide B 5-15 part and dabigatran etcxilate 100-400 part;
Preferably, the weight proportion of the two is: ginkalide B 8-12 part and dabigatran etcxilate 150-300 part; Further preferably, the weight proportion of the two is: ginkalide B 10 parts and dabigatran etcxilate 200 parts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510714240.2A CN105560236B (en) | 2014-10-30 | 2015-10-28 | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and non-peptide batroxobin inhibitor |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410604970 | 2014-10-30 | ||
| CN2014106049702 | 2014-10-30 | ||
| CN201510714240.2A CN105560236B (en) | 2014-10-30 | 2015-10-28 | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and non-peptide batroxobin inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105560236A true CN105560236A (en) | 2016-05-11 |
| CN105560236B CN105560236B (en) | 2019-03-15 |
Family
ID=55871260
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510714240.2A Active CN105560236B (en) | 2014-10-30 | 2015-10-28 | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and non-peptide batroxobin inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105560236B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102209544A (en) * | 2008-11-11 | 2011-10-05 | 贝林格尔.英格海姆国际有限公司 | Method for treating or preventing thrombosis using dabigatran etexilate or a salt thereof with improved safety profile over conventional warfarin therapy |
-
2015
- 2015-10-28 CN CN201510714240.2A patent/CN105560236B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102209544A (en) * | 2008-11-11 | 2011-10-05 | 贝林格尔.英格海姆国际有限公司 | Method for treating or preventing thrombosis using dabigatran etexilate or a salt thereof with improved safety profile over conventional warfarin therapy |
Non-Patent Citations (1)
| Title |
|---|
| 陈玉昆主编: "《萜类天然产物的提取及生产工艺》", 31 October 2009 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105560236B (en) | 2019-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2018086498A1 (en) | Pharmaceutical composition and application thereof | |
| JPH0372427A (en) | Medicine for thrombosis and its production | |
| JP2006511538A (en) | Use of a combination comprising a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a cytochrome P450 inhibitor such as a protease inhibitor | |
| US20230277523A1 (en) | Methods for inhibiting phosphate transport | |
| CN113521072A (en) | Application of nelfinavir in preparing medicine for preventing and treating non-alcoholic steatohepatitis and/or anti-hepatic fibrosis | |
| CN105560236A (en) | Pharmaceutical composition containing ginkgolide B and pseudo-peptide thrombin inhibitor and preparation method and application of pharmaceutical composition | |
| CN112891362B (en) | Pharmaceutical composition for treating sepsis and application thereof | |
| ES2423944T3 (en) | Use of megestrol acetate for the improvement of cardiac function and the treatment of coronary insufficiency | |
| CN113893242A (en) | Use of ASH in myocardial protection | |
| CN105456256A (en) | Medicinal composition containing bilobalide B and vitamin K antagonist as well as preparation method and application of medicinal composition | |
| CN105560238B (en) | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and phosphodiesterase inhibitors | |
| CN106822899B (en) | Medicine for promoting myocardial regeneration by inhibiting autophagy | |
| CN110898052A (en) | Application of kaempferol in preparation of medicine for treating sepsis | |
| CN105456279A (en) | Medicinal composition containing bilobalide B and prostaglandin cyclooxygenase of blood platelet as well as preparation method and application of medicinal composition | |
| CN105561309A (en) | Pharmaceutical composition containing ginkgolide B and thrombin inhibitor and preparation method and application of pharmaceutical composition | |
| KR101968190B1 (en) | Pharmaceutical composition containing ginkgolide b and xa factor inhibitor, preparation method thereof and use thereof | |
| CN102755319B (en) | Pharmaceutical composition containing prasugrel and carvedilol, and purpose thereof | |
| CN103203009A (en) | New application of partial metabolite of pentapeptide in preparation of myocardial ischemia resistant product | |
| CN105561308A (en) | Pharmaceutical composition containing ginkgolide B and adenosine diphosphate receptor antagonist and preparation method and application of pharmaceutical composition | |
| JPH04108731A (en) | Anti-aids viral agent | |
| CN108042525B (en) | Pharmaceutical composition for treating ventricular remodeling after myocardial infarction | |
| CN103690555A (en) | Pharmaceutical composition for treating acetyl cholinergic urticaria | |
| CN107496441B (en) | Use of cyclodextrins for the treatment and/or prevention of sepsis | |
| WO2022132786A1 (en) | Methods and compositions for treating pericarditis | |
| US20100286074A1 (en) | Pharmaceutical use of ginsenoside or mixture thereof and pharmaceutical composition of ginsenoside and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 610000 Wenjiang, Sichuan Province, Chengdu Strait science and Technology Development Zone Development Zone Applicant after: CHENGDU BAIYU PHARMACEUTICAL CO., LTD. Address before: 611130, Sichuan Wenjiang District, Chengdu Province, Chengdu Strait science and technology production area development zone Applicant before: Chengdu Baiyu Technology Pharmaceutical Co.,Ltd. |
|
| COR | Change of bibliographic data | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: The invention relates to a pharmaceutical composition containing Ginkgolide B and non peptide thrombin inhibitor and a preparation method and application thereof Effective date of registration: 20220316 Granted publication date: 20190315 Pledgee: Bank of Guiyang Limited by Share Ltd. Chengdu branch Pledgor: CHENGDU BAIYU PHARMACEUTICAL Co.,Ltd. Registration number: Y2022980002594 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |